Antitumor Therapy under Hypoxic Microenvironment by the Combination of 2-Methoxyestradiol and Sodium Dichloroacetate on Human Non-Small-Cell Lung Cancer. (23rd October 2020)

• Record Type: Journal Article
• Authors: Romero, Yair; Castillejos-López, Manuel; Romero-García, Susana; Aguayo, Alfonso Salgado; Herrera, Iliana; Garcia-Martin, Misael O.; Torres-Espíndola, Luz Maria; Negrete-García, Maria Cristina; Olvera, Angel Camarena; Huerta-Cruz, Juan Carlos; Velázquez-Cruz, Rafael; Cisneros, José; Soto, Edgar Flores; Solís-Chagoyán, Héctor; Mendoza-Milla, Criselda; Cabello-Gutiérrez, Carlos; Ruiz, Víctor; Aquino-Gálvez, Arnoldo
• Other Names: Ciobica Alin Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2020(2020)
• Publication Date: 2020-10-23
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2020/3176375
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : A hypoxic microenvironment is a hallmark in different types of tumors; this phenomenon participates in a metabolic alteration that confers resistance to treatments. Because of this, it was proposed that a combination of 2-methoxyestradiol (2-ME) and sodium dichloroacetate (DCA) could reduce this alteration, preventing proliferation through the reactivation of aerobic metabolism in lung adenocarcinoma cell line (A549). A549 cells were cultured in a hypoxic chamber at 1% O2 for 72 hours to determine the effect of this combination on growth, migration, and expression of hypoxia-inducible factors (HIFs) by immunofluorescence. The effect in the metabolism was evaluated by the determination of glucose/glutamine consumption and the lactate/glutamate production. The treatment of 2-ME (10 μ M) in combination with DCA (40 mM) under hypoxic conditions showed an inhibitory effect on growth and migration. Notably, this reduction could be attributed to 2-ME, while DCA had a predominant effect on metabolic activity. Moreover, this combination decreases the signaling of HIF-3 α and partially HIF-1 α but not HIF-2 α . The results of this study highlight the antitumor activity of the combination of 2-ME 10 μ l/DCA 40 mM, even in hypoxic conditions.